Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses either orally or via a nasogastric (NG) tube or intravenously (i.v).

Fibrosing cholestatic hepatitis (FCH) is characterized by progressive jaundice with a rapid decline in liver function leading to liver failure, most often associated with markedly elevated viral levels detected in the bloodstream (e.g. more than 20 times pre-liver transplantation levels) and in the liver tissue as well. The presence of FCH was reported based on the diagnosis given by the investigator.

Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had a liver re-transplant or died.

Treated acute rejection is defined as an acute rejection, clinically suspected, whether biopsy-proven or not, which has been treated and confirmed by the investigator according to the response to therapy. BPAR was defined as a treated acute rejection confirmed by biopsy. The local pathologist graded biopsies according to the Banff (1997) criteria. A sub-clinical rejection was defined as a rejection identified by center driven biopsy, i.e. a biopsy performed routinely at some pre-defined time points after transplantation as per center practice in the absence of any clinical signs of rejection.

BPAR was defined as a treated acute rejection confirmed by biopsy. The local pathologist graded biopsies according to the Banff (1997) criteria. Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had a liver re-transplant or died.

Cirrhosis was resulted due to the recurrence of the hepatitis C virus infection in the transplanted liver.

Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis.

The mean value (in Units per liter, IU/L) of following tests were calculated at 1 year post-transplant:

• Serum glutamic pyruvic transaminase (SGPT)
• Serum Glutamic Oxaloacetic Transaminase (SGOT)
• Bilirubin
• Alkaline Phosphate
• γ-Glutamyltransferase (GGT)

HCV RNA was measured (IU/µL)centrally pre-transplant (Day 1) and at 48 hours (Day 3), Day 8 and 29, Month 6 and 12 post-transplant and concomitantly to any additional biopsies performed.

Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. An increase of at least 1 stage demonstrated a worsening of the disease, i.e. the transition from one score to the next higher one.

Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. The mean score was equivalent to mean of IK at 1 and 2 years (evolution over time).

Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.

Total of all reporting groups

Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.

The number of participants with combined end point of death or graft loss or presented with a Ishak-Knodell fibrosis score (FS) ≥2 was calculated. Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had liver retransplant or died. Assessment of hepatic fibrosis was performed with liver biopsies read centrally. Ishak-Knodell FS was used to stage liver disease; 0=none; 1=portal fibrosis (some); 2=portal fibrosis (most); 3=bridging fibrosis (few); 4=bridging fibrosis (many); 5=Incomplete cirrhosis; 6=cirrhosis. Higher score indicates greater fibrosis.

Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.

Fibrosing cholestatic hepatitis (FCH) is characterized by progressive jaundice with a rapid decline in liver function leading to liver failure, most often associated with markedly elevated viral levels detected in the bloodstream (e.g. more than 20 times pre-liver transplantation levels) and in the liver tissue as well. The presence of FCH was reported based on the diagnosis given by the investigator.

Intent-to-treat population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.

Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had a liver re-transplant or died.

Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.

Treated acute rejection is defined as an acute rejection, clinically suspected, whether biopsy-proven or not, which has been treated and confirmed by the investigator according to the response to therapy. BPAR was defined as a treated acute rejection confirmed by biopsy. The local pathologist graded biopsies according to the Banff (1997) criteria. A sub-clinical rejection was defined as a rejection identified by center driven biopsy, i.e. a biopsy performed routinely at some pre-defined time points after transplantation as per center practice in the absence of any clinical signs of rejection.

Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.

BPAR was defined as a treated acute rejection confirmed by biopsy. The local pathologist graded biopsies according to the Banff (1997) criteria. Graft loss was considered to have occurred when allograft was presumed to be lost if a patient had a liver re-transplant or died.

Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.

Cirrhosis was resulted due to the recurrence of the hepatitis C virus infection in the transplanted liver.

Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.

Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis.

The Intent-To-Treat (ITT) population consisted of all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment.

The mean value (in Units per liter, IU/L) of following tests were calculated at 1 year post-transplant:

• Serum glutamic pyruvic transaminase (SGPT)
• Serum Glutamic Oxaloacetic Transaminase (SGOT)
• Bilirubin
• Alkaline Phosphate
• γ-Glutamyltransferase (GGT)

Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment. "n" is number participants with assessable data in each category.

HCV RNA was measured (IU/µL)centrally pre-transplant (Day 1) and at 48 hours (Day 3), Day 8 and 29, Month 6 and 12 post-transplant and concomitantly to any additional biopsies performed.

Intent-to-treat (ITT) population: all patients as randomized that were transplanted, received at least one dose of study drug and had at least one post-baseline efficacy assessment. "n" in each of the categories is the number of participants with data at the given time point.

Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. An increase of at least 1 stage demonstrated a worsening of the disease, i.e. the transition from one score to the next higher one.

The outcome measure was not analyzed because of premature termination of study.

Assessment of hepatic fibrosis was performed with liver biopsies at Day 1, Month 6, 12 and 24, read centrally by two independent pathologists blinded to treatment arm and time of biopsy. Ishak-Knodell score was used to stage liver disease; 0= None; 1= Portal fibrosis (some); 2= Portal fibrosis (most); 3= Bridging fibrosis (few); 4= Bridging fibrosis (many); 5 = Incomplete cirrhosis; 6 = Cirrhosis. Higher score indicates greater fibrosis. The mean score was equivalent to mean of IK at 1 and 2 years (evolution over time).

This outcome was not analyzed because of premature termination of study.

Tacrolimus was administered within the first 24 hours post-transplantation at an initial dose of 0.1-0.15 mg/kg/day in 2 divided doses (twice daily at 12-hour interval) either orally or via a nasogastric (NG) tube or intravenously (i.v). Twice daily (b.i.d.) administration was maintained throughout the study period. During the course of the study, the dose of tacrolimus was adjusted as necessary to achieve and maintain the C0 tacrolimus concentrations within target ranges.